Effect of leflunomide on sciatic nerve of adult albino rats: a histological and immunohistochemical study

ABSTRACT

Leflunomide is a commonly used disease-modifying antirheumatic drug. Potential clinical neurotoxic symptoms in patients treated with leflunomide in daily practice have been reported recently. It is unclear whether leflunomide is directly related to the occurrence of such nerve toxicity or whether other factors may be involved. This study was carried out to demonstrate the effect of leflunomide on sciatic nerve experimentally. For this purpose, 17 adult albino rats were used and were divided into three groups a control group [five rats], the second group [seven rats], which received 2 mg/kg body weight of leflunomide orally once daily for 8 weeks, and the third group [five rats], which received 2 mg/kg body weight of leflunomide orally once daily for 8 weeks and left for 4 weeks withdrawal. Sciatic nerve specimens were processed for histological study by light microscopy, electron microscopy, and immunohistochemistry. The light microscopy data were morphometrically analyzed in the sciatic nerves of the groups. We observed splitting of myelin lamellae, presence of marked intramyelinic edematous clefts between the split myelin lamellae, infolded myelin loops, and myelin degeneration. Changes in the axons included formation of myelin rings and figures in some of the larger axons, degeneration, compression, irregularity, and shrinkage. Therefore, it is recommended that patients under leflunomide treatment should be regularly examined for neurophysiological effects of leflunomide on peripheral nerves